CR4 - Scientific Panel

1. Exercise vs CR.

• “party line” is that exercise doesn’t mimic CR – it does help with your life time ‘functionality’ and performance, certainly
• Much of the research is either anecdotal or it uses inbred mice that are essentially the same individual (could just be individual variations – those selected subjects happened to respond well to exercise)
• Exercise must be voluntary – studies often were shocking the mice to make them run which introduced an additional stressor
• Studies were done with CRed animals that also exercised, but they died early which could have been because net caloric intake might have been far too low after adding the exercise component

2. Stressed animals via CR (with glucocorticoid level) – is this good?

• after eating, insulin and chaperones spike
• heat shock proteins (? Didn’t get this discussion)

3. Glucose & metabolism levels

• after eating, marked increase of RQ towards 1. before eating, it approached .7
• CR animals did not slow down metabolism per gram of LBM, some even increased
• no studies have been done to correlate body temp with metabolism, fat layer thickness

4. What’s gonna kill CRONies?

• low relative risk of long term degenerative diseases, but there is still genetic input
• hip fracture after age of 50 has survival rate of 50% (in general population)
• (what about building muscle?) should having extra muscle be a legitimate protection strategy against acute injury?
• do CRONies really have “high quality” bones? How can that be legitimized vs the known condition of slow wound healing?

5. Mouse mutations (dwarfism) extend life moreso than CR. What can be extrapolated from this, if anything? (missed some of this response)

6. Mice with a 100% predetermined genetic disease fatality expectation STILL lived longer when their cages had toys.

• We have fun already, so this might be another reason why the mouse studies are too different from human studies – they don’t truly mimic real life.

7. Funding sources – are they really drying up and how best to fight this?

• call your politicians to tell them to fund the NIH
• also what about giving honorariums, awards to those that are doing large amounts of CR research, funded by the society?
• doing other long term CRONie studies – difficult because little is controlled amongst us as a group – there are too many variations
• Josh mentioned wanting to start a “revival” and pledge $10k to establish new funding on the condition that the CR society have a scientific advisory panel to design valid research and then allocate the money.
• Individual microarray studies – would the participants get back some gene data that would be useful to them in a way to entice monetary participation in the study? Answer is NO, but….in just a few years, getting your own gene profile will probably cost just a thousand dollars or so.

8. Studies on dementia

• they can be difficult to perfectly test in mice since they cannot be queried like humans about their memory, etc.

9. Aubrey talked about the problem of our pre-selected group

• either they were already on CR for awhile before joining Luigi’s study, or they were eating healthily or near-CR immediately before going to full CR anyway. Better to get “true” samples of people who are average humans before they start CR but after they are interested enough to want to do it and participate in the study?

10. Is there a physiological aspect to repairing damage within the body that localizes that repair or is it a more systemic amount of change that could also involve….

11. Why does the body get stronger in the face of challenge? Why are we not getting stronger when not under stress? These questions can be answered as adaptive response – you react to a specific stress with a specific response. No stress, no response…. And we always have something in reserve – hidden potential that must be flushed out.

12. Pathology of death in CRed individuals

• highly varied but of course everyone has to die of something.
• fragility goes up as extreme age is achieved
• unseen fatal factors come more into play, such as arythmmia, etc
• rats at the end of their life show wide variations in food intake but all dropped a lot of weight before dying

13. Warren suggests running these studies against identical twins to attempt to mimic the rat studies which used inbred strains.